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Документ Changes in nitric oxide production and development of oxidative stress in rats heart during prolonged triptorelin-induced central deprivation of luteinizing hormone synthesis(Poltava State Medical University, Poltava, 2022) Voroshilova, T. A.; Shepitko, V. I.; Stetsuk, Ye. V.; Akimov, O. Ye.; Puzyryov, G. S.; Ворошилова, Тетяна Анатоліївна; Шепітько, Володимир Іванович; Стецук, Євген Валерійович; Акімов, Олег Євгенович; Пузирьов, Гай СергійовичCentral deprivation of luteinizing hormone synthesis for 365 days leads to the development of oxidative stress in rat hearts. The peak of oxidative damage to the heart under these conditions happens on the 180th day of the central deprivation of luteinizing hormone synthesis. Production of nitric oxide during central deprivation of luteinizing hormone synthesis undergoes complex changes from an initial decrease of NO-synthase-dependent nitric oxide production on the 30th and 90th day to overproduction of nitric oxide from NO-synthases on the 365th day of the experiment.Документ Changes in the microcirculatory bed of the liver during alcoholic hepatitis modeling(Полтавський державний медичний університет, 2023) Mykytenko, A. O; Akimov, O. Ye.; Yeroshenko, G. A.; Shevchenko, O. M.; Neporada, K. S.; Микитенко, Андрій Олегович; Акімов, Олег Євгенович; Єрошенко, Галина Анатоліївна; Шевченко, О. М.; Непорада, Каріне СтепанівнаIt is well known that chronic alcohol consumption leads to multiple organ damage and microcirculation disorders of organs and tissues. The aim of the work was to study the morphometric indicators of the microcirculatory bed of rat liver during alcoholic hepatitis modeling. The experiments were performed on 30 white, mature male Wistar rats, weighing 180–220 g. The animals were divided into 2 groups: I – control; group II– animals, on which we modeled alcoholic hepatitis according to Yu.M. Stepanov. (2017). The diameter of the sinusoidal capillaries around the central vein and the hepatic triad was increased at all time points compared to the control. The diameter of the lumen of the central vein of the hepatic lobe of rats increased on the 1st, 5th and 7th day of the experiment. The diameter of the lumen of the interlobular artery of rats was decreased during the studied periods, and the interlobular vein was increased. The diameter of the lumen of the arteriole increased on the 3rd day of the experiment, and the diameter of the lumen of the venule of the lobule of the rats decreased on the 1st day of the experiment. The microcirculatory channel of the liver of rats under the conditions of simulation of chronic alcoholic hepatitis in the first week demonstrates an increase in the exchange of metabolites between the central vein and the vein of the triad, which is accompanied by their expansion and threatens the development of venous hyperemia.Документ Dynamics of CD68 receptor expression in macrophages of the interstitial space of the rat testis under triptorelin prolonged administration(Ukr. Biochem. J., 2023) Stetsuk, Ye. V.; Shepytko, V. I.; Akimov, O. Ye.; Boruta, N. V.; Rud, M. V.; Pelypenko, L. B.; Lysachenko, O. D.; Vilkhova, O. V.; Skotarenko, T. A.; Voloshyna, O. V.; Стецук, Євген Валерійович; Шепітько, Володимир Іванович; Акімов, Олег Євгенович; Борута, Наталія Володимирівна; Рудь, Марія Володимирівна; Пелипенко, Лариса Борисівна; Лисаченко, Ольга Дмитрівна; Вільхова, Олена Вікторівна; Скотаренко, Тетяна АнатоліївнаTestosterone, the production of which is stimulated by the release of luteinizing hormone (LH) has a remarkable anti-inflammatory and immunomodulatory effect, and in conditions of testosterone deficiency tissue damage can occur due to excessive differentiation of macrophages into a proinflammatory M1 phenotype. The aim of this study was to determine the spread of CD68 receptors as the marker of inflammation on the cells in the interstitial space and testicular vessels under LH synthesis blockade with tryptorelin. Sexually mature white male rats were randomly divided into control (10 animals) and experimental (25 animals) groups. Animals in the experimental group were injected with a tryptorelin acetate solution (0.3 mg/kg). Immunochemical analysis of CD68+ expression was estimated at Olympus FV10i-LIV laser scanning confocal microscope using fluorescent labeling dye. It was shown that luteinizing hormone deprivation led to an increase in the distribution of the CD68 receptor in the interstitial space and in the testicular vessels from day 30 to 180 of the experiment, associated with the increase of inducible NO synthase activity in testis tissue.Документ Effect of combined nitrate-fluoride intoxication on the function of NO-synthases and arginases in the gastric mucosa, blood and heart of rats(JSciMed Central®, 2016) Akimov, O. Ye.; Kostenko, V. O.; Костенко, Віталій Олександрович; Акімов, Олег ЄвгеновичThe focus of this article is on the functioning of NO-synthases and arginases in the gastric mucosa, blood and heart of white rats under excessive intake of sodium fluoride and sodium nitrate during 30 days. Excessive intake of sodium nitrate was modeled by infusion of aqueous solution into stomach through special catheter at a dose of 500 mg / kg. Excessive intake of sodium fluoride was modeled by infusion of aqueous solution into stomach through special catheter at a dose of 10 mg / kg. The activity of these enzymes was measured by spectrophotometric methods. Analysis of the influence produced by combined nitrate-fluoride intoxication on total NOS activity in the gastric mucosa, heart and blood showed the presence of antagonistic effect of nitrates and fluorides. Nitrates act as NOS inhibitors, whereas the fluorides are inducers of NOS. Under their combined action in the organism, fluoride-induced elevation prevails over nitrate-induced inhibition, but only in tissue homogenates. Such effect is absent in blood. The inductive effect of combined nitrate-fluoride intoxication on functioning of arginases is mediated by nitrate release of L-arginin from NOS. Combined intoxication showed prevalence of inducing influence of nitrates over inhibiting effect of fluoridesДокумент Extracellular matrix of rat liver under the conditions of combining systemic inflammatory response syndrome and chronic alcohol intoxication(Полтавський державний медичний університет, 2022) Mykytenko, A. O.; Akimov, O. Ye.; Yeroshenko, G. A.; Neporada, K. S.; Микитенко, Андрій Олегович; Акімов, Олег Євгенович; Єрошенко, Галина Анатоліївна; Непорада, Каріне СтепанівнаThe aim of this study was to establish the effect of systemic inflammatory response syndrome on the background of chronic alcohol intoxication on the concentration of oxyproline, glycosaminoglycans and sialic acids in the liver of rats. The study was performed on 24 male Wistar rats. Animals were divided into 4 groups of 6 animals: I – control; II – systemic inflammatory response syndrome group; III – alcoholic hepatitis groupand IV – animals with a combination of systemic inflammatory response syndrome and chronic alcohol intoxication. The concentrations of glycosaminoglycans, heparin-heparan, keratan-dermatan and chondroitin fractions of glycosaminoglycans, free oxyproline and sialic acids were studied in the liver tissue homogenate. The combination of systemic inflammatory response syndromeand chronic alcohol intoxication leads to ncreased intensity of collagenolysis, glycoprotein catabolism and reduced intensity of breakdown of proteoglycans of connective tissue of the liver. However, it changes the ratio of individual fractions of glycosaminoglycans in the direction of reducing тtheconcentration of anti-inflammatory and increasing regenerative.Документ Functioning of no-cycle in the saliva of children with type 1 diabetes mellitus(ДУ «Інститут проблем ендокринної патології ім. В. Данилевського НАМН України», 2021) Kuz, I. O.; Akimov, O. Ye.; Kostenko, V. O.; Sheshukova, O. V.; Maksymenko, A. I.; Pysarenko, O. A.; Кузь, Ірина Олексіївна; Акімов, Олег Євгенович; Костенко, Віталій Олександрович; Шешукова, Ольга Вікторівна; Максименко, Аліна Іванівна; Писаренко, Олена АнатоліївнаIntroduction. The presence of type 1 diabetes mellitus in children is a major risk factor for periodontal disease. The aim of research work was to determine the activity of NO-synthase and arginase in saliva in children age with insulin-dependent diabetes mellitus. Materials and methods. We examined 82 children including 56 children with type 1 diabetes mellitus and 26 children without somatic diseases. NO-synthase (NOS) activity was determined by the difference in nitrite concentration before and after incubation of tissue homogenate. Determining arginase activity was based on analysis the difference in the concentration of L-ornithine before and after incubation in phosphate buffer solution. Statistical processing of the results was performed with the help of Real Statistics extension for Microsoft Excel. The significance of the differences between groups was estimated by Khruskal-Wallis ANOVA test with following paired comparison by Mann-Whitney test. Research results and their discussion. The violation of the indicators’ balance between groups of healthy children with healthy gums and children with diabetes mellitus and healthy gums showed us a decrease in regenerative capacity in the mucous membrane in persons with type 1 diabetes mellitus. Increased ARG activity in group of children with type 1 diabetes mellitus and chronic catarrhal gingivitis may lead to rivalry between NOS and ARG for L-arginine. Increased ARG activity in group of somatically healthy children with chronic catarrhal gingivitis and children with type 1 diabetes mellitus and chronic catarrhal gingivitis compared with group of healthy children with healthy gums indicated an adaptive response aimed at repairing gum damage. Based on this, increased NO production from NOS is a consequence of insulin deficiency (systemic factor). Conclusions. The combination of systemic factor (type 1 diabetes mellitus) and local (chronic catarrhal gingivitis) leads to dysregulation of the NO-cycle and increasing of competition between NOS and ARG.Документ Hemical changes in the extracellular matrix of rat liver during chronic alcohol intoxication(Полтавський державний медичний університет, 2022) Mykytenko, A. O.; Akimov, O. Ye.; Yeroshenko, G. A.; Shevchenko, O. M.; Neporada, K. S.; Микитенко, Андрій Олегович; Акімов, Олег Євгенович; Єрошенко, Галина Анатоліївна; Шевченко, Олена Миколаївна; Непорада, Каріне СтепанівнаExcessive alcohol consumption is a global health problem worldwide, resulting in more than 3 million deaths each year. The purpose of this work was to study the biochemical markers of intercellular matrix metabolism of rat liver under the conditions of chronic alcohol intoxication modeling. The experiments were performed on 30 male Wistar rats, weighing 180-220 g. The animals were divided into 2 groups: І – control; ІІ – chronic alcohol intoxication. Animals were removed from the experiment on days 10, 14, 21 and 28. We studied concentration of glycosaminoglycans, oxyproline and sialic acids in rat liver. We established that the greatest depolymerization of proteoglycans was on the 21st day, the highest intensity of collagenolysis was on the 14th day. Glycoproteins underwent the greatest catabolism on the 28th day. Chronic alcohol intoxication on the 28th day led to increased breakdown of glycoproteins and proteoglycans of the extracellular matrix of the liver, and increased the intensity of collagenolysis.Документ Influence of carboline on reactive oxygen and nitrogen species production in gastric mucosa of rats under chronic nitrate-fluoride intoxication(Національний фармацевтичний університет, 2018-10-18) Akimov, O. Ye.; Акімов, Олег ЄвгеновичCertain regions of Ukraine have risk of simultaneous intake of excessive concentrations of nitrates and fluorides with drinking water and food. Fluorides can enter groundwater since they are byproduct of aluminum production. Some regions of Ukraine have high concentration of fluorides in groundwater due to high concentration of fluorine containing salts in ground. Poltava region can serve as good example of such regions. Nitrates are used as cheap and effective fertilizers. Therefore vegetables are the primary source of excessive nitrates intake. Gastro-intestinal system is the first target for adverse effects of both mentioned above environmental pollutants during their alimentary consumption. Combined effect of nitrates and fluorides on gastro-intestinal system is not well researched. The aim of this study is to determine influence of “Carboline” on production of superoxide anion radical (O2˙-) and peroxynitrite (ONOO-) in rats gastric mucosa under chronic nitrate-fluoride intoxication. Materials and methods. Experiment was performed on 38 Wistar rats weighting 180-230 g. Animals were divided into 3 groups: control group (10), combined intoxication group (15) and “Carboline” group (13). Chronic nitrate-fluoride intoxication (combined intoxication) was induced as described in our previous work [1]. Animals of “Carboline” group were receiving suspension of “Carboline” at a dose 100 mg/kg during combined intoxication induction. Animals were sacrificed under thiopental anesthesia by bloodletting. All biochemical studies were performed in 10% tissue homogenate. Production of O2˙- was determined as described in [2]. Production of ONOO- was determined by increase in concentration of peroxynitrites of alkali and alkali-base metals after 40 min incubation in buffer solution (ph=7.4). Concentration of peroxynitrites of alkali and alkali-base metals was determined as described in [1]. Results were analyzed by Mann-Whitney method. Differences between groups were deemed statistically significant if p<0.05. Results and discussion. Combined intoxication increases production of O2˙- by 195% compared to control group. Production of ONOO- elevates by 17.64%. Suspension of “Carboline” decreases O2˙- production by 21% compared to combined intoxication group. Production of ONOO- drops by 25%. Increased O2˙- production during combined intoxication owns to the fact that both nitrates and fluorides can influence mitochondrial electron transport chain. There are evidences in literature that fluoride ions can cause tissue hypoxia by impairing mitochondrial electron transport. However exact mechanism is not known yet. Cytochromes of mitochondria have ability to reduce nitrates to nitrites sacrificing two electrons in the process. Under physiologic conditions electrons from cytochromes should be used in ATP synthesis. Two electron reduction of nitrates to nitrites in eukariotic cells does not lead to ATP synthesis. This “electron leakage” creates possibility of uncoupling of oxidative phosphorylation and ATP synthesis thus leading to O2˙- production by mitochondria. Judging from almost twofold increase in O2˙- production during combined intoxication we can assume that nitrates and fluorides have synergetic effect on O2˙- production. ONOO- is formed in reaction of O2˙- with nitric oxide (NO). Both nitrates and fluorides can lead to increased production of NO [1]. However sources of increased production of NO are different for fluorides and nitrates. Fluorides can increase NO production by activation of inducible NO-synthase, while nitrates can provide excessive amounts of NO by activation of nitrate reductases. “Carboline” is a sorbent which consists from carbon fibers obtained by extrusion of crushed tissue carbon fiber sorbent of AUT –M brand. “Carboline” has sorption surface of 2500 sq. meters per 1 gram, which allows it efficiently absorb nitrates and fluorides from gastro-intestinal tract. Conclusion. Suspension of “Carboline” is effective for correction of increased reactive oxygen and nitrogen species production in gastric mucosa of rats under nitrate-fluoride intoxication.Документ Influence of NF-kB on the development of oxidative-nitrosative stress in the liver of rats under conditions of chronic alcohol intoxication(Інститут біохімії ім. О. В. Палладіна НАН України, 2022) Mykytenko, A. O.; Akimov, O. Ye.; Yeroshenko, G. A.; Neporada, K. S.; Микитенко, Андрій Олегович; Акімов, Олег Євгенович; Єрошенко, Галина Анатоліївна; Непорада, Каріне СтепанівнаAlcohol-related liver disease is the most common cause of liver disease worldwide. The purpose of this work is the establishment of the influence of the transcription factor κB on the development of oxidative nitrosative stress in the liver of rats under conditions of chronic alcohol intoxication.Chronic alcohol intoxication led to increased production of reactive oxygen and nitrogen species on the background of decreased antioxidant activity, thus intensifying lipid peroxidation in the liver. Blockade of the transcription factor κB during chronic alcohol intoxication despite an increase in antioxidant activity and decrease of reactive oxygen and nitrogen species production did not ameliorate oxidative damage to the liver. Blockade of activation of nuclear transcription factor κB in rat liver by PDTC reduced the risk of oxidative damage to hepatocytes, but did not reduce the risk of developing nitrosative damage to hepatocytes.Документ Influence of prolonged central deprivation of testosterone synthesis on production of reactive oxygen and nitrogen species and morphological structure of rat testes(Українська медична стоматологічна академія, 2020) Stetsuk, Ye. V.; Akimov, O. Ye.; Shepitko, V. І.; Goltsev, A. М.; Стецук, Євген Валерійович; Акімов, Олег Євгенович; Шепітько, Володимир Іванович; Гольцев, Анатолій МиколайовичSome testicular diseases require long-term use of testosterone synthesis blockers. It is known that testosterone is a necessary component for the physiological cooperation of cell forms of the stroma and parenchyma of testes. The scientific literature contains a limited amount of data about the effect of long-term deprivation of testosterone synthesis on this cooperation. The aim of our study was to establish the effect of long-term (365 days) inhibition of hypothalamic-pituitary stimulation of spermatogenesis on morphological and biochemical parameters in rat testes. Central deprivation of testosterone synthesis leads to fibrosis with subsequent disruption of the structural organization of the convoluted seminiferous tubules, hemodynamic disorders, endothelial dysfunction, increased density of blood vessel walls and systemic congestion. A decrease in the activity of constitutive NO synthase isoforms plays a major role in the development of structural changes in the testes of rats.Документ Influence of prolonged tripterelin-induced central deprivation of testosterone synthesis on morphological structure of rat’s liver(Українська медична стоматологічна академія, 2021) Polyvyana, O. A.; Shepitko, K. V.; Stetsuk, Ye. V.; Akimov, O. Ye.; Dubinin, D. S.; Полив'яна, Олександра Анатоліївна; Шепітько, Костянтин Володимирович; Стецук, Євген Валерійович; Акімов, Олег Євгенович; Дубінін, Дмитро СергійовичIn recent years, the incidence of prostate cancer has increased worldwide. For example, in 2012, the GLOBOCAN project found that prostate cancer was the second most commonly diagnosed cancer and the fifth leading cause of cancer deaths among men worldwide. Insufficient testosterone can exacerbate liver damage caused by obesity. The aim of our study was to identify morphological changes in the liver of rats at the tissue and cellular levels, to study the processes of formation of reactive oxygen species and the intensity of lipid peroxidation during prolonged central deprivation of testosterone synthesis caused by triptereline. Triptorelin-induced central deprivation of testosterone synthesis leads to oxidative damage to hepatocytes due to increased production of reactive oxygen species and decreased activity of antioxidant enzymes. Oxidative damage to liver cells begins at the molecular and cellular levels and becomes apparent at the tissue level on day 180 of the central deprivation of testosterone synthesis.Документ Influence of quercetin on biochemical and morphological changes in rat testes after 30 days long central deprivation of luteinizing hormone(Полтавський державний медичний університет, 2021) Stetsuk, Ye. V.; Shepitko, V. I.; Akimov, O. Ye.; Yakushko, O. S.; Solovyova, N. V.; Стецук, Євген Валерійович; Шепітько, Володимир Іванович; Акімов, Олег Євгенович; Якушко, Олена Святославівна; Соловйова, Наталія ВеніамінівнаCentral blockade of luteinizing hormone synthesis by the injection of triptorelin acetate with parallel oral intake of quercetin on the 30th day of the experiment causes minor changes in the structure of the interstitial space of the rats’ testes and is characterized by variability in the populations of interstitial endocrinocytes and macrophages, which in our opinion, affects the change in the parameters of spermatogenesis in the rats’ testes. Quercetin protects tissue of rats’ testes from oxidative damage induced by triptorelin injection on 30th day of the experiment by increasing the antioxidant protection and reducing reactive oxygen species formation. Quercetin increase the arginase-dependent arginine cleavage, which was inhibited by triptorelin injection.Документ Influence of transcription factor κB on remodeling of extracellular matrix of rat liver under conditions of chronic alcohol intoxication(Полтавський державний медичний університет, 2022) Mykytenko, A. O.; Akimov, O. Ye.; Yeroshenko, G. A.; Neporada, K. S.; Микитенко, Андрій Олегович; Акімов, Олег Євгенович; Єрошенко, Галина Анатоліївна; Непорада, Каріне СтепанівнаLiver fibrosis is a common tissue reaction associated with chronic liver damage resulting from prolonged parenchymal cell damage and inflammation. The fibrogenic response is characterized by the progressive accumulation of extracellular matrix components enriched in collagen fibrils and impaired extracellular matrix remodeling. The aim of this study was to establish the effect of transcriptional factor κB on the concentration of oxyproline, glycosaminoglycans and sialic acids in the liver of rats under conditions of chronic alcohol intoxication. The study was performed on 24 male Wistar rats. The animals were divided into 4 groups of 6 animals: І – control; II – animals with inhibition of κB; ІІI – animals with chronic alcohol hepatitis and ІV – animals with κB inhibition on the background of chronic alcohol intoxication. We studied the total concentration of glycosaminoglycans, concentration of heparin-heparan, keratan-dermatan and chondroitin fractions of glycosaminoglycans, free oxyproline and sialic acids in the liver tissue homogenate. Prolonged alcohol intoxication of rats leads to remodeling of the extracellular matrix as evidenced by increased collagenolysis and catabolism of glycoconjugates of amorphous connective tissue of the liver. The use of the inhibitor of the transcription factor κB in the background of prolonged alcohol intoxication of animals reduced the concentration of GAG by 1.43 times, lowered oxyproline concentration by 1.6 times and decreased the concentration of sialic acids by 1.14 times compared to chronic alcohol intoxication group. Transcriptional factor NF-κB under conditions of chronic alcohol intoxication affects the architectural remodeling of connective tissue of rat liver by increasing degradation of collagen fibers and destruction of glycoproteins and proteoglycans of the extracellular matrix.Документ Morphofunctional features of rat testes interstitial endocrinocytes and sustentocytes after 90 days of central testosterone synthesis deprivation(Українська медична стоматологічна академія, 2020) Stetsuk, Ye. V.; Akimov, O. Ye.; Shepitko, K. V.; Goltsev, A. N.; Стецук, Євген Валерійович; Стецук, Евгений Валерьевич; Акімов, Олег Євгенович; Акимов, Олег Евгеньевич; Шепітько, Костянтин Володимирович; Шепитько, Константин Владимирович; Гольцев, Анатолій Миколайович; Гольцев, Анатолий НиколаевичWith the social system development, there is a tendency to change attitudes towards family and family values. In developed European countries, there is a trend towards high sexual activity in elderly men and late creation of a family with children, which undergoes certain difficulties in connection with a decreased testosterone production in later years. The purpose of the study was to establish the microscopic organization of rat interstitial endocrinocytes and sustentocytes, to determine the sources of nitric oxide production and the intensity of oxidative stress in the testes with experimental central deprivation of testosterone synthesis with diphereline on the 90th day of the experiment. The experiments were carried out on 20 sexually mature male white rats of the Wistar line. Rats were divided into 2 groups: the control group (10) and the experimental group (10), which were injected subcutaneously with diphereline (Triptorelin embonate) at a dose of 0.3 mg / kg of the active substance for 90 days. Prolonged central deprivation of testosterone synthesis in animals leads to emergence of functional stress structural signs in population of sustentocytes and interstitial endocrinocytes, which are aimed to support testicular secretion. Central deprivation of testosterone synthesis within 90 days causes oxidative stress development owing to reactive oxygen species hyperproduction and nitrite accumulation in testicular tissue due to increased inducible NO-synthase activity;Документ Morphological and functional changes of the hepatic vascular bed Under the conditions of modeling alcoholic hepatitis(Полтавський державний медичний університет, 2021) Mykytenko, A. O.; Akimov, O. Ye.; Yeroshenko, G. A.; Neporada, K. S.; Микитенко, Андрій Олегович; Акімов, Олег Євгенович; Єрошенко, Галина Анатоліївна; Непорада, Каріне СтепанівнаThe experiments were performed on 30 white adult outbred male rats weighing 180–220 g. Animals were divided into 2 groups: I – control (n=6); II – animals with simulated alcoholic hepatitis (n=24). We studied the total NO synthase activity, peroxynitrite, nitrites and nitrosothiols concentrations in rat liver homogenate. We also studied morphometric parameters of hemomicrocirculatory tract of the rat liver. On the 7th day of modeling of alcoholic hepatitis interparticle arteries and veins and lobular arterioles narrow. The central vein dilates. The sinusoidal capillaries around the hepatic triad and central vein dilate. Alcoholic hepatitis increases the total activity of NO synthases, the concentration of peroxynitrites and nitrosothiols, but reduces the concentration of nitrites in the liver of rats on day 7 of the experiment. Nitric oxide and its metabolites play an important role in the regulation of the resistant part of the hemomicrocirculatory tract of the rat liver in the first three days of the experiment. Further redistribution of nitric oxide cycle metabolites leads to an increase in the concentration of peroxynitrite, which is a factor of secondary alteration; Експерименти виконані на 30 білих статевозрілих безпородних щурах-самцях, вагою 180-220 г. Тварини були розділені на 2 групи: І – контрольна (n=6); ІІ група – тварини, яким моделювали алкогольний гепатит (n=24). В гомогенаті печінки щурів визначали активність загальної NO-синтази, концентрації пероксинітриту, нітритів та нітрозотіолів. Також визначали морфометричні параметри емомікроциркуляторного русла печінки щурів. На 7 добу моделювання алкогольного гепатиту міжчасточкові артерії і вени, часточкові артеріоли звужуються. Центральна вена розширюється. Синусоїдні капіляри навколо печінкової тріади і центральної вени розширяються. Алкогольний гепатит збільшує загальну активність NO-синтаз, концентрацію пероксинітритів та нітрозотіолів, проте знижує концентрацію нітритів у печінці щурів на 7 добу експерименту. Оксид азоту і його метаболіти грають важливу роль в регуляції резистентної ланки гемомікроциркуляторного русла печінки щурів перші три доби експерименту, подальший перерозподіл метаболітів циклу оксиду азоту призводить до збільшення концентрації пероксинітриту, який виступає фактором вторинної альтерації.Документ Morphological changes and oxidative homeostasis in the liver tissues during long central deprivation of luteinizing hormone synthesis by triptorelin(Полтавський державний медичний університет, 2021) Polyvyana, O. A.; Shepitko, V. I.; Stetsuk, Ye. V.; Akimov, O. Ye.; Yakushko, O. S.; Voloshyna, O. V.; Полив'яна, Олександра Анатоліївна; Шепітько, Володимир Іванович; Стецук, Євген Валерійович; Акімов, Олег Євгенович; Якушко, Олена Святославівна; Волошина, Олена ВалеріївнаIn recent years, researchers have focused on the problem of the dependence of the functioning of various organs and systems on the level of androgens. The effect of long inhibition of testosterone synthesis by triptorelin on liver tissue is poorly understood. The aim of this research was to establish the microscopic organization of rat livers, production of nitric oxide and the intensity of oxidative stress in the rat livers during experimental central deprivation of luteinizing hormone synthesis by diphereline injection on the 270-360th day of the experiment. The experiments were carried out on 30 sexually mature male white rats of the Wistar line. Rats were divided into 2 groups: the control group (10) and the experimental group (20). Animals from the experimental group were subcutaneously injected triptorelin at a dose of 0.3 mg of the active substance/ per kg of body weight for 360 days, while the control group received an injection of saline. It was found that oxidative stress develops in hepatocytes, which is morphologically confirmed by karyopyknosis of the nuclei, oxyphilia of the cytoplasm with the appearance of a significant number of vacuoles in it. The vessels of the microcirculatory bed react with stasis. An increase in the production of superoxide radical anion in rat liver may be due to the absence of an inhibitory effect of testosterone on macrophages and liver mitochondria, which is accompanied by depletion of antioxidant enzymes and the development of oxidative stress. The intensity of biochemical markers of oxidative stress on the 360th day is lower than on the 270th day, which is due to an increase in the activity of antioxidant enzymes and a decrease in the production of reactive oxygen species.Документ Morphological changes in rat liver structure during central deprivation of lutheinizing hormone synthesis at 365th day of experiment(Полтавський державний медичний університет, 2022) Rud, M. V.; Shepitko, V. I.; Stetsuk, Ye. V.; Akimov, O. Ye.; Рудь, Марія Володимирівна; Шепітько, Володимир Іванович; Стецук, Євген Валерійович; Акімов, Олег ЄвгеновичMacrophages play a central role in both tissue homeostasis and inflammation. Understanding the origin, development and involvement of tissue-resident macrophages in the regulation of homeostatic processes is fundamental to the development of future intervention strategies to modulate macrophage functions in specific areas. Resident liver macrophages include Kupffer cells, which together with sinusoidal cells and Ito cells form a significant population of non-parenchymal, antigen-presenting cells. The androgen / androgen receptor (AR) interaction plays a role in the development of the liver in the embryonic stage, the maximum dimorphism of the effects of androgen / AR occurs after puberty due to the activity of the hypothalamic-pituitary-gonadal axis. Quercetin effect on the inflammatory process is explained by the blockade of the lipoxygenase pathway of arachidonic acid metabolism, reduced synthesis of leukotrienes. The aim of our study was to determine the qualitative and quantitative changes in Kupffer cells during chemical castration of male rats of central origin, which was caused by the introduction of a solution of triptorelin acetate. And also to elucidate the results of the quercetin action on antigen-presenting liver cells on the background of the effects caused by the use of triptorelin solution. The experiments were performed on 30 adult male white rats. Rats were divided into 3 groups: control (10), experimental 1 (10) and experimental 2 (10). Animals from experimental group 1 were injected subcutaneously with triptorelin acetate at a dose of 0.3 mg of active substance per kg of body weight. Animals from experimental group 2 received triptorelin acetate in the same dosage and quercetin 100 mg per kg body weight 3 times a week. Changes in the liver of animals from group 1 occur on cellular and subcellular levels, causing minor venous stasis, erythrocyte sludge and macrophage infiltration. Concomitant oral administration of quercetin minimizes structural and morphological changes in rat liver tissue by increasing the antioxidant protection of liver tissue.Документ Peculiarities of connective tissue degradation in rat’s liver on early terms of chronic alcoholic hepatitis modelling(Українська медична стоматологічна академія, 2021) Mykytenko, A. O.; Akimov, O. Ye.; Yeroshenko, G. A.; Микитенко, Андрій Олегович; Акімов, Олег Євгенович; Єрошенко, Галина АнатоліївнаThe article deals with the peculiarities of connective tissue degradation in rat liver on early terms of chronic alcoholic hepatitis modelling. Modeling of chronic alcoholic hepatitis leads to the development of oxidative stress in rat liver tissues due to a decrease in the activity of antioxidant enzymes and an increase in the production of reactive oxygen species. As a result of the development of oxidative stress in the liver of rats in the first stages of modeling alcoholic hepatitis, the concentration of the anti-inflammatory heparin-heparan fraction of glycosaminoglycans decreases, the accumulation of keratan-dermatan and chondroitin fractions of glycosaminoglycans occurs. The processes of degradation of the fibrous components of the liver’s connective tissue increase and the concentration of the sulfide anion decreases.Документ Role of nitric oxide in development of fibrotic changes in rats’ testes after 270 day central deprivation of testosterone synthesis(Українська медична стоматологічна академія, 2020) Stetsuk, Ye. V.; Akimov, O. Ye.; Shepitko, K. V.; Boruta, N. V.; Goltsev, A. M.; Стецук, Евгений Валерьевич; Акимов, Олег Евгеньевич; Шепитько, Константин Владимирович; Борута, Наталия Владимировна; Гольцев, Анатолий Николаевич; Стецук, Євген Валерійович; Акімов, Олег Євгенович; Шепітько, Костянтин Володимирович; Борута, Наталія Володимирівна; Гольцев, Анатолій МиколайовичDisturbance in production of nitric oxide (NO) may lead to various changes in different organs and systems. Certain clinical situations require prolonged usage of inhibitors of testosterone synthesis. Scientific literature provides limited information regarding the influence of prolonged deprivation of testosterone synthesis on production of NO and microscopic organization of rats’ testes. Prolonged central deprivation of testosterone synthesis leads to endothelial dysfunction, development of fibrosis, decreases the nitric oxide production and shifts pro-/antioxidant balance in favor of the pro-oxidants without increase in lipid peroxidation intensity. Central deprivation of testosterone synthesis leads to fibrosis with subsequent disruption of the structural organization of the convoluted seminiferous tubules, hemodynamic disturbances, endothelial dysfunction, increased density of the vascular wall of blood vessels and systemic stasis. Decreased production of NO from constitutive isoforms of NO-synthase plays major role in development of structural changes in the interstitial tissue of testes on the 270th day of the experiment.Документ Structural organization of stromal and parenchymal components of rat testes during central deprivation of testosterone synthesis on the 180 day of the experiment(Українська медична стоматологічна академія, 2020) Стецук, Євген Валерійович; Стецук, Евгений Валерьевич; Stetsuk, Ye. V.; Акімов, Олег Євгенович; Акимов, Олег Евгеньевич; Akimov, O. Ye.; Шепітько, Костянтин Володимирович; Шепитько, Константин Владимирович; Shepitko, K. V.; Гольцев, Анатолій Миколайович; Гольцев, Анатолий Николаевич; Goltsev, A. M.Prolonged central deprivation of testosterone synthesis may lead to biochemical and morphological changes in testes. Influence of prolonged testosterone deficiency on reactive nitrogen and oxygen species production, morphological changes in interstitial endocrinocytes and sustentocytes is not yet fully understood. The number of interstitial endocrinocytes is reduced in comparison with the control group, there are interstitial spaces between the convoluted tubules with a complete absence of interstitial endocrinocytes. Interstitial endocrinocytes are reduced in size, their nuclei are heterochromic. When we studied the structural organization of rat sustentocytes from the experimental group in comparison with the control group, we found that hyperplasia of the elements of the smooth endoplasmic reticulum was observed in the cytoplasm of the sustentocytes. The number of mitochondria in the cytoplasm of the sustentocytes decreased, the electron density of the mitochondrial matrix was lowered, protein structures were present either inside the vacuoles or independently located in the cell cytoplasm. Biochemical studies revealed increased NO production from inducible NO-synthase and development of oxidative stress. Experimental central deprivation of testosterone synthesis with diphereline on the 180th day of the experiment leads to shift of NO synthesis from constitutive NO-synthases to inducible NO-synthase and intensification of oxidative stress due to increase of superoxide anion-radical production and decrease in antioxidant protection.
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